Prebiotic Lipidic Amphiphiles and Condensing Agents on the Early Earth
First Round of Evaluation
Round 1: Reviewer 1 Report and Author Response
The review article written by Fiore and Strazewski is an excellent revision of the prebiotic chemistry performed during the last 50 years toward the synthesis of protocell lipids. Particularly appealing is their rationalization about the relationships between synthetic pathways toward complete lipids, the different possible sources and roles of phosphorylating reagents, and the generality of cyanamide and derivatives as condensing agents of different prebiotic reactions that include the phosphorylation of long-chain alcohols. Such analysis allows obtaining a very necessary and complete picture of how intricate the network of reactions that lead to complete lipids, as well as to oligopeptides and oligonucleotides, is.
Hence, the review is perfectly suitable to be published in Life and its publication is strongly recommended, provided that a few minor issues are addressed.
1) The resolution of Figures 1-3 is low, and thus should be improved.
2) Some words should be dedicated to the discussion about abiotic / biotic evolution of lipids. That is, it is not clear what the lipid composition of the cenancestor membrane was. Surely, lipids of certain complexity were available by then, yet they probably kept evolving in complexity until nowadays. An important question within the field is then to establish the boundary between the pre-biological and the Darwinian evolutionary processes of lipids.
3) In page 2, line 61, the authors claim that life, as a chemical system, is(among other features listed in the same sentence to characterize it). I would say this is not correct, as death surely proves for all living entities. Perhaps it is more correct to say that living systems are “self-sustained, dynamic,and far from thermodynamic equilibrium”.
4) In the last sentence of section 2, the authors argue about a hypothetical “proto-metabolism” that may be behind the origins of amino acids, nucleotides and lipids. However, there is controversy and various reasons why the network of reactions described in ref. 35 should not be called a “proto-metabolism”. Such work is of course of great importance, because it connects the chemistry toward the main bio-monomers, but this aspect should at least be tinged or put into context when reviewing it.
Author Response
1) Concerning the resolution of figures 1-3 and 4 please see the .tif files that we are sending together with the submission of the revised version of the manuscript. For the drawings in table 1 please see the corresponding Chemdraw file. For a better comprehension we have revised figures 2 and 3.
2) Text lines from 103 “An implicit assumption…” to 114 “…or eliminate instead.” were added according to the following suggestions: “Some words should be dedicated to the discussion about abiotic / biotic evolution of lipids. That is, it is not clear what the lipid composition of the cenancestor membrane was. Surely, lipids of certain complexity were available by then, yet they probably kept evolving in complexity until nowadays. An important question within the field is then to establish the boundary between the pre-biological and the Darwinian evolutionary processes of lipids.”
3) As suggested, we replaced “irreversible” by “kinetically stable” in line 70
4) Concerning your comments: “In the last sentence of section 2, the authors argue about a hypothetical “proto-metabolism” that may be behind the origins of amino acids, nucleotides and lipids. However, there is controversy and various reasons why the network of reactions described in ref. 35 should not be called a “proto-metabolism”. Such work is of course of great importance, because it connects the chemistry toward the main bio-monomers, but this aspect should at least be tinged or put into context when reviewing it.” we modified the end of section 2 (lines 84-93) as follows : we expand this part by separating the contribution of Eschenmoser & Loewenthal, from those of Sutherland, and add in the end “…, irrespective so far of the precise energetics or the identification of any autocatalytic or crosscatalytic feedback loops”.
Consequently, we reformulated a similar sentence in subsection 4.1 Conclusions, lines 432-434: “…integral part of…”.
Round 1: Reviewer 2 Report and Author Response
The review entitled “Prebiotic Lipidic Amphiphiles” fully covers the interesting topic on the prebiotic synthesis of amphiphiles. However the text needs to be improved before the review is accepted for publication and specifically:
1. The manuscript is difficult to follow being not-readable, primarily because the authors use long paragraphs in writing the review. Thus the text should be thoroughly edited.
2. Rewrite the “Conclusion and prospective” section including what are really the conclusions and prospects of the study and transfer in the main text the remaining information.
Author Response
1) The manuscript was thoroughly re-edited, and many but not all long sentences have been shortened.
2) Section 6, Conclusions and Perspectives, have been split into two subsections 6.1 and 6.2. We modified in subsection 6.2 a few expressions for the sake of clarity.
Round 1: Reviewer 3 Report and Author Response
This is a knowledgeable review of lipid chemistry related to prebiotic conditions and the origin of cellular life. For the most part the text is well written and some novel perspectives are presented. The abstract, however, should be carefully edited because it has incomplete sentences and some poor grammatical constructions.
Although I would quibble with some of the points the authors make, there are no major problems and I would be happy to see the manuscript published as it stands.
Author Response
The abstract was fully re-edited according to your suggestions.
